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Oesophageal cancer research

All treatments must be fully researched before they can be adopted as standard treatment for everyone. This is so that we can be sure they work better than the treatments we already use. And so we know they are safe. First of all, treatments are developed and tested in laboratories. Only after we know that they are likely to be safe to test are they tested in people, in clinical trials. Cancer Research UK supports a lot of UK laboratory research into cancer and also supports many UK and international clinical trials.

Why research is important

All treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so that

We can be sure they work

We can be sure they work better than the treatments that are available at the moment

They are known to be safe

First of all, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either on the NHS or privately. Cancer Research UK supports a lot of UK laboratory research into cancer.

Tests in patients are called clinical trials. Cancer Research UK supports many UK and international clinical trials.

There are 4 phases of clinical trials. This is fully explained in the understanding clinical trials section. If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials recruiting in the UK. If there is a trial you are interested in, print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team. The database also has information about closed trials and trial results.

All the new approaches covered here are the subject of ongoing research. Until studies are completed and there is evidence that a new treatment is better than the current standard treatment, these treatments cannot be used as standard therapy for cancer of the oesophagus.

Research into preventing oesophageal cancer

Using drugs or diet to try to reduce the chance of cancer developing is called chemoprevention. Various anti inflammatory drugs have been studied to try to prevent cancer development. Some studies have shown that aspirin reduces the risk of oesophageal cancer. But aspirin can cause serious side effects in some people, especially if it is taken regularly, so researchers are continuing to look into using other drugs.

Some studies have shown that people who take drugs to lower cholesterol (statins) have a lower risk of oesophageal cancer compared to people who don't take them. But more research is needed to confirm this.

Another known risk factor for cancer of the oesophagus is diet. Some countries have a higher rate of oesophageal cancer. This may be because of the foods they eat. There is a lot of research going on into why and how certain foods may increase the risk of cancer of the oesophagus and other types of cancer. As oesophageal cancer is more common in China and Japan, a lot of research looks into smoked, fermented or pickled foods that are popular in these countries. Drinking very hot liquids has also been linked to oesophageal cancer in some studies.

Although there are other more established risk factors for oesophageal cancer, scientists have found another possible risk factor for this type of cancer. It is a virus called the human papilloma virus (HPV). HPV is known to be linked to cervical cancer. There are many different types of HPV, and some of these (including types 16 and 18) have been linked to cancer of the oesophagus, particularly to squamous cell cancers. But the exact role of HPV in the development of oesphageal cancer is not yet clear.

Researchers have used a technique called polymerase chain reaction (PCR) to pick up HPV infection in the DNA of body cells. In future, we may be able to use this type of test to find people more at risk of developing oesophageal cancer. Researchers in America are even trying to develop a vaccine based on HPV16 that could be used to treat oesophageal cancers that carry HPV16. More research is needed before we will know how strongly HPV is linked to oesophageal cancer.

The HALO trial is looking at using heat from radio waves to destroy abnormal cells in the food pipe. The treatment is called radiofrequency ablation. The abnormal cells may be Barrett’s oesophagus or changes in the squamous cells called squamous dysplasia. If left untreated, these changes may become cancerous in some people after some time. The trial wants to find out how well radiofrequency ablation may work at removing Barrett's oesophagus or squamous dysplasia and preventing oesophageal cancer.

Research into Barrett’s oesophagus

Barrett's oesophagus is a condition where cells lining the oesophagus have become abnormal, but are not yet cancerous. It is caused by acid coming back up the food pipe from the stomach (acid reflux). People with Barrett’s have a slight risk of going on to develop oesophageal cancer. They usually have an endoscopy every 2 years to check the cells in the lining of the oesophagus.

There is no easy screening test available at the moment. A pilot study called the BEST study recently looked at a new screening tool called the cytosponge for people with a high risk of developing Barrett’s oesophagus. The researchers used a sponge on a string that people swallowed to collect cell samples from the inner lining of the oesophagus. Results from this study showed that this new test is safe and acceptable, and looks like it could work for screening.

The BEST2 study is looking at a larger number of people to see how well the cytosponge works as a screening test for people at high risk of developing Barrett's oesophagus. Some people who have already been diagnosed with Barrett's oesophagus are also taking part in this study. The researchers are looking for cell changes that can develop into oesophageal cancer and markers that may show which people are at a higher risk of Barrett’s oesophagus becoming cancer. They hope this will help them to know which people with Barrett's oesophagus may need close monitoring or treatment.

The ChOPIN study is looking at why some people with Barrett’s get cancer and others don’t. This may help them to prevent it in the future. Or it may help to lead to a better understanding of risk factors, so that we may be able to develop screening for people at the highest risk.

Some studies have suggested that an inherited faulty gene can cause Barrett’s oesophagus to develop. A study is looking at people who have Barrett’s oesophagus and their families. The researchers hope to learn more about what causes this condition and what the risk to family members might be. This study has closed and we are waiting for the results.

ESD is a new procedure to remove high grade Barrett's oesophagus or a very early oesophageal cancer. It is similar to another procedure to remove the lining of the oesophagus called an endoscopic mucosal resection (EMR). The main difference between the 2 techniques is that with an EMR the abnormal area is cut out in several pieces whereas with ESD the abnormal area is removed whole with a margin of healthy tissue around it.

In 2010, the National Institute of Health and Care Excellence (NICE) issued guidance on ESD. As the procedure is quite new, it is not yet clear how well it works and what the side effects are. So patients should only be offered this treatment as part of a trial.

Other researchers are looking into using esomeprazole, with or without aspirin, as a way of stopping Barrett’s oesophagus turning into cancer. Esomeprazole is a type of drug called a proton pump inhibitor (PPI). It reduces the amount of acid produced by the stomach. Doctors think that esomeprazole may help to prevent Barrett's oesophagus developing into cancer. But they are not sure yet how well it will work.

Doctors think that irritation from stomach acid causes the cell changes in the oesophageal lining. So if the amount of stomach acid you produce is lowered, this may help to protect the cells near where the oesophagus joins the stomach. Aspirin is included in this trial because there is some evidence that it may help prevent cancer. There have been separate trials for men and women looking into this.

Researchers in the USA have had promising results using cryotherapy to treat Barrett's oesophagus once the oesophageal cells have started to change. They put a small tube into the throat, and use liquid nitrogen to freeze these cells before they can become cancerous. The damaged cells will fall off, allowing normal cells to replace them. This treatment is being used in some hospitals in the USA, but larger studies and long term results are needed.

A pilot study called BRIDE is comparing 2 endoscopy procedures called radiofrequency ablation and argon plasma coagulation in people with Barrett's oesophagus. Both procedures work by gently burning the affected tissue and allow the lining to heal normally. Both seem useful treatments, but doctors do not know which is best. Researchers in this study will try to work this out. This study has closed and we are waiting for the results.

People with Barrett's oesophagus usually have regular check ups called endoscopies. The doctor takes about 10 to 20 samples of tissue (biopsies) from your oesophagus. These are sent off to the lab and checked to see if the cells are getting more abnormal. This usually takes about 3 weeks. The BOOST study is looking at a new technique called an optical biopsy. This may be able to tell doctors straight away if the cells in your oesophagus have become more abnormal, or if there are any cancer cells present.

If the optical biopsy is as good as endoscopy at picking up cell changes, it could mean that people with Barrett's oesophagus will need to have less biopsies in future.

The BOSS study is looking at whether it is better to monitor people with Barrett's oesophagus every 2 years or to wait until they have a change in their symptoms. This study has closed and we are waiting for the results.

The TIME trial is looking at a new type of endoscopy called ETMI (Endoscopic Tri-Modal Imaging) to help study cell changes in people with Barrett's oesophagus. Usually endoscopes use a white light to show up areas of abnormal tissue. But ETMI has special filters for green and blue light to show up changes that white light can't. The researchers are also using a tiny microscope to help see cell changes. They will take biopsies to look for features (markers) that are linked to abnormal cell changes that lead to cancer. The researchers hope that information from these tests will help them to develop a test to diagnose Barrett's oesophagus more easily and work out who is at high risk of developing cancer.

A study is looking for DNA in the blood of people with Barrett's oesophagus or oesophageal cancer. Looking for DNA in a patient's bloodstream to monitor disease may be more effective, more accurate and more convenient than repeated endoscopies. The researchers want to find out at what stage of disease development these pieces of DNA show up in the blood. They also want to develop a blood test that will be able to tell if abnormal cells or early oesophageal cancer has come back after being removed by endoscopy or surgery, and to monitor the disease in those having chemotherapy. This study has closed and we are waiting for the results.

Gene tests before treatment

Doctors can use chemotherapy, radiotherapy and surgery or a combination of these to treat oesophageal cancer. The treatment the doctor chooses depends on the size of the cancer and how far it has grown. But doctors cannot easily tell which treatment will work best for each person. They are always looking for ways to improve treatment. Doctors now have a way of looking at a very large number of genes in cancer cells. This is called gene expression profiling. Researchers are looking at genes in oesophageal cancers to see if this can help them work out who is most likely to benefit from certain treatments.

When you have surgery to remove an oesophageal cancer, your surgeon will take out all the lymph nodes nearest to the tumour and your food pipe. This is because they may contain cancer cells, which could continue to grow. So removing them can lower the risk of the cancer coming back in the future. If there is a reason to suspect that lymph nodes further away also contain cancer cells, your surgeon will remove these nodes too.

There is a lot of debate around the world about whether routinely taking out more lymph nodes would lower the risk of the cancer coming back even more. Trials have been done to try to show whether or not taking out lymph nodes further away from the cancer can lower recurrence rates.

We don’t have the research evidence yet to say that taking out more lymph nodes routinely will help people. Doctors have to weigh up the possible increased side effects against the likely benefit. There is no point in doing more complicated surgery if it isn’t going to help. We are not aware of any UK trials looking at this at the moment.

Researchers in this study are looking at a way of checking sentinel nodes. They will inject a radioactive tracer close to the cancer, allowing it to travel to the lymph nodes. They will then use a special keyhole gamma probe to show up the first lymph nodes reached. If a keyhole (laparoscopic) technique to find and test the sentinel lymph nodes is accurate, it could be used in future to reduce the amount of surgery you need to remove lymph nodes, reducing the risks that come with it. This study has closed and we are waiting for the results.

A pilot study called ROMIO is looking at how practical it would be to run a large trial comparing traditional surgery with keyhole (laparoscopic) surgery, or a combination of the two, to treat oesophageal cancer. The aim of the main study is to compare how well each type of surgery works in terms of recovery, health related quality of life, cost and how long people live after surgery. This pilot study is testing this out on a small scale, to work out how practical it would be to recruit lots of people later on.

Light therapy (PDT)

Photodynamic therapy (PDT) uses light to kill cancer cells. You first take a drug that makes your body cells sensitive to light. Then the doctor shines a very bright light onto the cancer cells. This activates the drug and kills the cells. PDT is sometimes used for cancer of the oesophagus. Doctors may use it in some cases for advanced cancer, to shrink a blockage in the food pipe. There is information about PDT for advanced oesophageal cancers in this section.

PDT has been studied in people with stage 1 cancer of the oesophagus. Researchers hope it might be an alternative treatment for people not well enough to have surgery. The National Institute for Health and Care Excellence (NICE) have issued guidance on PDT for early oesophageal cancer. They say that this treatment is quite new, and there are still uncertainties about how well it works, particularly in the long term. NICE suggest that doctors can offer patients this treatment, but they should tell you all about the benefits and drawbacks first. Your doctor should make sure you understand that this is a new treatment that is still being tested.

NICE also recommend that doctors follow up patients who've had PDT to see how well they do. Doctors should enter patients into clinical trials if possible. This will all help in finding out how well PDT works in treating early oesophageal cancer, particularly in the longer term. Also, different drugs have been tested for use with PDT.

Researchers are looking into treating both low grade and high grade Barrett’s oesophagus with PDT. They hope that this treatment will destroy the abnormal cells and so stop cancer from developing in the first place. NICE have issued guidance to doctors about using PDT to treat high grade Barrett's oesophagus. Overall, most of the patients in clinical studies looking into PDT have done well. The very abnormal (high grade) cells went away. NICE say that people should be followed up long term after this treatment. They say there is not enough evidence at the moment to show how well this treatment works for low grade Barrett's. We need to carry on testing it and following up patients for longer before we know how well it can prevent oesophageal cancer from developing.

Chemotherapy

Many clinical trials are underway testing combinations of newer chemotherapy drugs, and giving chemotherapy alongside other treatment such as radiotherapy or biological therapy. Doctors also continue to study chemotherapy drugs already used to treat oesophageal cancer. For example looking at different doses, in different combinations or at different ways of giving them. The aim of this type of research is to get better results when treating oesophageal cancer with chemotherapy. This is quite complicated because the research has to be carried out for different stages of cancer. For example, just because a combination of chemotherapy drugs helps with advanced cancer doesn’t necessarily mean that it will help to stop your cancer coming back if you have the same treatment before surgery.

The OE05 trial is comparing 2 combinations of chemotherapy before surgery for oesophageal cancer. These combinations are Cisplatin and 5FU (CF) and ECX. Doctors want to find out which is the best combination to use before surgery. This trial has closed and we are waiting for the results.

In past trials, a combination called ECF has been very effective for advanced oesophageal and stomach cancers. This combination is made up of epirubicin, cisplatin and 5FU. But doctors are continuing to try to improve the effectiveness and find better ways of giving treatment. 5FU is now available as tablets, as a drug called capecitabine (Xeloda). So doctors are now testing ECX, which is epirubicin, cisplatin and capecitabine. Other combinations being looked at also have epirubicin and either 5FU or capecitabine, but with another drug called oxaliplatin instead of cisplatin.

A clinical trial called REAL 2 compared the chemotherapy drugs 5FU with capecitabine, and cisplatin with oxaliplatin in stomach and oesophageal cancer that has already spread. The results showed that capecitabine worked as well as 5FU, and oxaliplatin worked as well as cisplatin. And the quality of life of people on the different chemotherapy treatments was similar.

The GO2 trial is looking at the best way to treat people with cancer of the oesophagus or stomach who are not strong enough to have standard chemotherapy. For some people, chemotherapy with 3 drugs is too strong and so it may be better to give a milder form of chemotherapy. For others it may be better not to have chemotherapy at all, but to have treatment to manage symptoms (best supportive care). The researchers for this trial are looking at giving 2 out of 3 standard chemotherapy drugs. They are oxaliplatin and capecitabine (OxCap). Some people will have the drugs at the same doses as standard treatment, and others will have reduced doses. Some people won't have any chemotherapy, but will have best supportive care.

In a small trial, doctors have been testing ECF chemotherapy with a drug called decitabine, which may make the cancer cells more sensitive to treatment. This is an early phase trial and the people taking part have advanced oesophageal cancer. This trial has closed and we are waiting for the results.

Some research has been carried out with drugs called taxanes (docetaxel (Taxotere) and paclitaxel (Taxol)) in advanced oesophageal cancer. The results are promising but more research needs to be done to compare this treatment with the drugs that are currently considered standard treatment.

The COUGAR-02 trial looked at how well docetaxel worked for oesophageal cancer or stomach cancer that had come back after chemotherapy. The researchers found that on average people who had docetaxel lived longer than people who just had treatment to control symptoms.

One research trial is looking at blood samples from people having ECF chemotherapy for oesophageal cancer. Differences in certain genes and proteins can affect the way that cancers grow and spread. The differences can also affect how well chemotherapy works. So a trial is looking at many proteins and the DNA in the liquid part of the blood (serum). The researchers hope this will help to understand more about how treatments work. This trial has closed and we are waiting for the results.

A study is looking at how chemotherapy affects your level of fitness. Some hospitals routinely use a heart and lung test called a cardiopulmonary exercise test (CPET). This is to measure your fitness before surgery. The researchers in this study want to use CPET to measure fitness before and after chemotherapy. They also want to find out how people are after surgery. The aim of this study is to find out if CPET can predict whether someone will be fit for surgery after having chemotherapy. The study has now closed and we are waiting for the results.

Chemotherapy and radiotherapy together

Evidence suggests that people who have chemotherapy and radiotherapy together (chemoradiotherapy) before surgery may do better. A paper looking at all the different trial results together, showed that survival rates 2 years after treatment improved by 13 out of every 100 patients (13%) who had chemoradiation before surgery.

It is important to realise that not every person treated will benefit. Researchers sometimes work out how many people need to have a new treatment to make sure that one cancer death is prevented. For this treatment in oesophageal cancer, they worked out that 1 extra person will survive for every 8 treated. Like all statistics, this is an average and no one can predict what will happen to any one person. This combined treatment may be particularly suitable for squamous cell cancers. While it helps adenocarcinomas, these also respond well to chemotherapy on its own before surgery. It's also important to remember that chemoradiotherapy is an intensive treatment and has significant side effects.

Research is still going on into this combined treatment for other situations in oesophageal cancer. Researchers are looking at chemoradiation

Before surgery in cancers too advanced to remove, to try to make surgery possible

After surgery to try to lower the risk of cancer coming back

The Neo SCOPE trial is comparing 2 different combinations of chemotherapy drugs alongside radiotherapy for oesophageal cancer. Everybody taking part has oxaliplatin and capecitabine chemotherapy to begin with followed by chemoradiation. The researchers are comparing the chemo drugs oxaliplatin and capecitabine with paclitaxel and carboplatin, alongside radiotherapy. They want to find out how well each combination works and to learn more about the side effects. They also want to see if it would be possible to do a larger trial comparing chemoradiation with chemotherapy before surgery, and which drug combination is best to use.

Biological therapies

Biological therapies act on processes in cells or change the way that cells signal to each other. They can stimulate the body to attack or control the growth of cancer cells. There is detailed information about biological therapies in our cancer treatment section.

Cells signal to each other by making and releasing proteins called growth factors. The growth factors encourage the cells to grow and multiply. The growth factors lock into other proteins, called receptors, on the cells' surface. Once the receptor has its growth factor locked in, it fires a signal into the cell, telling it to grow and divide into more new cells.

Cancer cells commonly make too much of many of these proteins. If we can block these proteins, we may be able to stop or slow down the growth of cancer cells. Some growth factor blockers are called tyrosine kinase inhibitors (TKI) because they block growth factor enzymes called tyrosine kinases. An example of a TKI is gefitinib (Iressa). It blocks one of the receptors, called epidermal growth factor receptor or EGFR. The phase 3 COG trial looked at gefitinib for people with advanced oesophageal cancer. The trial team found that oesophageal cancer took longer to start growing again in people taking gefitinib compared to a dummy drug (placebo). But there was no difference in the average length of time people lived (overall survival) between the 2 groups. You can read the results of the COG trial on our clinical trials database.

The LEO trial is a phase 2 trial looking at another tyrosine kinase inhibitor called lapatinib (Tyverb). It works by blocking HER2 receptors on cancer cells that trigger their growth. The trial is testing whether adding lapatinib to chemotherapy helps people before surgery for cancer of the oesophagus. It also wants to find out it is helpful to start lapatinib before chemotherapy. This trial has closed and we are waiting for the results.

The phase 1DEBIOC trial is looking at a drug called AZD8931 alongside chemotherapy for oesophageal cancer or cancer where the oesophagus meets the stomach (gastro oesophageal junction cancer). The researchers want to find the highest dose of AZD8931 you can safely have with chemotherapy. And to see if AZD8931 and chemotherapy is better than chemotherapy alone for these types of cancer.

PARP inhibitors are drugs that block a protein in cells, called PARP. This protein is important for cells to repair their DNA. By stopping PARP from repairing DNA damage, cancer cells die. Doctors are looking at a PARP inhibitor called olaparib for a number of different cancers, including oesophageal cancer.

The ROCOCO trial is an early trial looking at olaparib with radiotherapy for oesophageal cancer. People who are not able to have surgery for oesophageal cancer may have treatment with chemotherapy and radiotherapy together (chemoradiation). But you have to be in quite good health to be able to have this treatment. If not, you may have radiotherapy on its own. In this trial, doctors will be comparing radiotherapy alone to radiotherapy and olaparib together. The main aim of the trial is to find the highest dose of olaparib you can have safely alongside radiotherapy for oesophageal cancer.

This is very early research in oesophageal cancer. Vaccines in cancer treatment are usually used to try to stop the cancer from coming back after it has been treated. The vaccines are designed to try to make your immune system recognise and attack cancer cells. Cancer cells are foreign to the body, in that they are not normal cells. But they develop from normal cells originally, so it is difficult for your immune system to recognise them.

An early trial is looking at a vaccine based on a protein called CEA (carcino-embryonic antigen). The cells of many different cancer types make too much CEA, including some cancers of the oesophagus. This vaccine is designed to make the immune system seek out cells with too much CEA and kill them. This trial has closed and we are waiting for the results.

There is a lot of research going on into the use of monoclonal antibodies (MABs) to treat cancer. MABs are proteins, made in the laboratory from a single copy of a human antibody. Monoclonal just means all of one type.

They act in the same way as immune system proteins that seek out and kill foreign matter in your body, such as bacteria and viruses. MABs are designed to recognise abnormal proteins on the outside of cancer cells.

Bevacizumab (Avastin) is another type of MAB. It works by blocking a protein on the cells called vascular endothelial growth factor (VEGF). This protein helps cancers to grow blood vessels, so they can get food and oxygen. Without a blood supply, the cancers starve and cannot grow. The ST03 trial is looking at bevacizumab for oesophageal and stomach cancer and cancer where the food pipe meets the stomach (the gastro oesophageal junction). The researchers are comparing bevacizumab and chemotherapy with chemotherapy alone, both before and after surgery.

Ramucirumab has been looked at in an international phase 3 trial for gastro oesophageal junction cancers and stomach cancers which had continued to grow after chemotherapy. The researchers for the REGARD trial compared ramucirumab and best supportive care with a dummy drug (placebo) and best supportive care. The trial team found the average length of time people lived (overall survival) was longer in the group who had ramucirumab compared to the group who had the placebo.

Another international phase 3 trial recently looked at ramucirumab with paclitaxel chemotherapy for advanced gastro oesophageal junction cancers and stomach cancers. The researchers for the RAINBOW trial found that the people who had ramucirumab and paclitaxel lived longer on average compared to the people who had chemotherapy alone.

The SCOPE1 trial looked at another type of MAB called cetuximab with chemoradiation for oesophageal cancer. The trial team found that adding cetuximab to chemoradiation did not help people with oesophageal cancer and caused more side effects, especially skin problems.

A trial is looking at a drug called onartuzumab alongside chemotherapy for cancer of the gastro oesophageal junction. The people taking part have cancer that has spread to another part of the body and has only small amounts of the HER2 protein (it is HER2 negative). Onartuzumab targets a receptor called Met that is found on cancer cells. The researchers want to find out if the combination of onartuzumab and chemotherapy is better than chemotherapy alone for HER2 negative cancer, and to learn more about the side effects. This trial has now closed and we are waiting for the results.

Treatment for symptoms in advanced cancer

Many people with oesophageal cancer have difficulty swallowing. This can affect your eating, physical activity and quality of life. One of the treatments for difficulty swallowing is to put a plastic or metal tube, called a stent, into the food pipe where the blockage is. This keeps the food pipe open and makes swallowing easier. Unfortunately, after some time the cancer may grow over the stent and swallowing becomes difficult again.The ROCS trial is looking at giving radiotherapy after having a stent put in, to see if the benefits of the stent last longer.

The BioStent study is looking at dissolvable (biodegradable) stents and radiotherapy to treat problems with swallowing. Biodegradable stents are put in the same way as metal stents but dissolve within 3 to 4 months.The people taking part in the study then have a short course of radiotherapy. The researchers hope the biodegradable stent will give rapid relief of symptoms, and the radiotherapy will give longer term relief. The aims of the study are to see how well this treatment plan works and what people think of it. The researchers want to see if it works well enough to plan a larger trial to compare biodegradable stents and radiotherapy with using metal stents.

Cachexia seems to be linked to the production of body chemicals called cytokines. Cancers can produce cytokines in larger amounts than normal. The cytokines can then cause the body to break down fat and muscle faster than normal.

Researchers think that thalidomide may be able to help with cachexia as it can reduce the amount of cytokines in the body. Early trial results have been promising, but no one is quite sure yet how well it works.

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